Prostate cancer continues to be a significant health problem, both domestically and worldwide. Numerous studies have demonstrated the efficacy and safety of transperineal prostate brachytherapy in the therapy of prostate cancer. The success of brachytherapychiefly depends on our ability to intra-operatively tailor the radiation dose to the patient's individual anatomy. Thus the objective of this research is to design, develop, and clinically test a method for intra-operative localization of the implanted seeds in relation to the prostate, to allow for intra-operative dosimetric optimization and exit dosimetry.Brachytherapy is predominantly performed with transrectal ultrasound guidance, which provides adequate real-time visualization of soft tissue anatomy, but does not showthe implanted seeds. To overcomethis problem, we propose registration of ultrasound to intra-operative C-arm fluoroscopy, wherethe implanted seeds will be reconstructed from fluoroscopy and superimposed on ultrasound. In particular, we will: (1) Design a system and workflow that is consistent with contemporary practice of prostate brachytherapy. (2) Developoptimized mathematical algorithms for reconstruction of seed implants from C-arm fluoroscopy images, spatial registration of fluoroscopy and ultrasound imaging. (3) Integrate the algorithms with an existing commercialprostate brachytherapy systemand implant optimization methods. (4) Conduct Clinical SystemPerformance Evaluation Trial on human patients. We have establishedthe technical feasibility of this approachin a Phase-1 SBIR research grant. We are requesting Phase-2 support to develop a clinical-grade system and evaluate its technical performanceon human patients. The resulting system will withstand the scrutiny of subsequent FDA approvaland enter wide-spread clinical use via commercial dispersion.